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Satoru Muto,1 Tadashi Okada,2 Moriyoshi Yasuda,3 Hidetsugu Tsubouchi,4 Koji Nakajima,4 Shigeo Horie1,5 1Department of Advanced Informatics for Genetic Disease, Juntendo University Graduate School of Medicine, Tokyo, 2Department of Clinical Development, 3Pharmacovigilance Department, 4Department of Medical Affairs, Otsuka Pharmaceutical Co, Ltd, 5Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan Aim: The aim of this trial (ClinicalTrials.gov identifier: NCT01280721) was to investigate the long-term safety profile of tolvaptan in Japanese patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This open-label multicenter trial was conducted to examine adverse drug reactions (ADRs) related to tolvaptan up to an additional 3 years in 135 Japanese patients who participated in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes (TEMPO) 3:4 trial at doses of 60–120 mg/d. Blood samples were collected at baseline; at weeks 1, 2, and 3; at month 3; and every 3 months thereafter. Results: In total, 134/135 (>99%) patients experienced ADRs. The most frequent ADRs were thirst (77.0%), pollakiuria (57.0%), polyuria (37.8%), and hyperuricemia (14.8%). Any unexpected ADRs were not reported in this trial. Most ADRs occurred early during treatment. Fourteen patients (10.4%) experienced hepatic events, and 8 (5.9%) experienced >3-fold increases above the upper limits of normal in serum alanine aminotransferase or aspartate aminotransferase levels between 3 and 9 months following tolvaptan initiation, which recovered after drug interruption. Of the 8 patients, 7 (5.2%) were previously allocated to the placebo arm in the TEMPO 3:4 trial and 4 (3.0%) discontinued due to the hepatic events. One patient (0.7%) was previously allocated to tolvaptan and experienced similar events in the TEMPO 3:4 trial. None of the hepatic ADRs met Hy’s Law laboratory criteria. Conclusion: ADRs observed in this extension trial were similar to those identified in the TEMPO 3:4 trial and hepatic events were not progressive. Keywords: autosomal dominant polycystic kidney disease, drug-induced liver injury, liver function test, safety profile, tolvaptan

Amr Abdelhamed,1,2 Shin-ichi Hisasue,1 Masato Shirai,3 Kazuhito Matsushita,1 Yoshiaki Wakumoto,1 Akira Tsujimura,1 Taiji Tsukamoto,4 Shigeo Horie1 1Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan; 2Department of Dermatology, Venereology and Andrology, Sohag University, Graduate School of Medicine, Sohag, Egypt; 3Department of Urology, Juntendo University Urayasu Hospital, Urayasu, Japan; 4Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan Background: Patients with late-onset hypogonadism (LOH) benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods: Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5) and aged males treated with testosterone replacement therapy (TRT group, n=5). Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP) and mean arterial blood pressure (MAP) ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results: Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant). The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant). The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103) µm2 in the control group and 4.93×103 (range 6.42–19.7×103) µm2 in the TRT group (not statistically significant). In contrast, median visceral fat cell size was significantly smaller in the TRT group (4.93×103 µm2 [range 0.51–14.88×103]) than in the control group (6.08×103 µm2 [0.77–19.97×103]; P

Muto S, Okada T, Yasuda M, et al. Drug Healthc Patient Saf. 2017;9:93–104.On page 97, ‘Discussion’ section, lines 10–13, left column, the sentence: ‘Similarly, placebo patients who crossed over onto active treatment discontinued at a similar rate (24.0%), while those who continued on tolvaptan treatment discontinued at a much lower rate (11.8%)’ should read: ‘Similarly, placebo patients who crossed over onto active treatment discontinued at a similar rate (26.0%), while those who continued on tolvaptan treatment discontinued at a much lower rate (10.6%)’. On page 101, Figure 6, the number of patients of ‘Completed trial’ in the TEMPO Extension Japan trial should be revised from ‘n=75’ to ‘n=76’, and ‘Withdrawal rate’ should also be revised from ‘11.8%’ to ‘10.6%’ in the allocated to tolvaptan in TEMPO 3:4 trial. The number of patients of ‘Completed trial’ in TEMPO Extension Japan trial should be revised from ‘n=38’ to ‘n=37’, and ‘Withdrawal rate’ should also be revised from ‘24.0%’ to ‘26.0%’ in the allocated to placebo in TEMPO 3:4 trial.Read the original article.

Background Menopausal symptoms are common among middle-aged women. Working women with severe menopausal symptoms are more likely to experience presenteeism—a condition where employees continue to work despite feeling unwell. However, it remains unclear as to which specific symptoms women experience during the menopausal transition and postmenopausal periods that primarily contribute to presenteeism. Aims To evaluate the associations between types of menopausal symptoms and presenteeism among Japanese women. Methods A cross-sectional study of 4000 women aged 40–59 years who were currently working was conducted in Japan in September 2022. We used an online self-administered questionnaire that included items on demographic characteristics, the Menopause Rating Scale for measuring menopausal symptoms and the Work Functioning Impairment Scale for measuring presenteeism. Logistic regression analysis was performed. Results Women with severe overall menopausal symptoms had 12.18-fold (95% confidence interval [CI] 9.09–16.33, P  < 0.001) increased odds of presenteeism compared with those without symptoms. Participants with psychological symptoms also had significantly higher presenteeism (severe: odds ratio: 9.18, 95% CI 6.60–12.78, P  < 0.001). However, after controlling for psychological symptoms, there were no significant associations between somatic and urogenital symptoms and presenteeism. Conclusions The results indicate that menopausal symptoms, especially psychological symptoms, have a significant impact on presenteeism among Japanese women. Organizations need to address menopausal symptoms in the workplace, with an emphasis on reducing work-related stress for women with menopausal symptoms. [ABSTRACT FROM AUTHOR]